Fall 2010 Research

Vincent Alessi'11 Ann Arbor, MI Advisor: Norman Craig

Honors Project: Synthesis of Isotopomers of cis- and trans-Hexatriene and High-Resolution Molecular Spectroscopy

Description: Deuterium and 13C isotopomers of the cis and trans isomers of 1,3,5-hexatriene, which are early members of the biologically important polyene series, are being synthesized, and ground state rotational constants are being found from the analysis of C-type bands in the high-resolution infrared spectra of the trans isomer and from microwave spectra for the cis isomer. From rotational constants and quantum chemical calculations, semi-experimental equilibrium structures will be found with the goal of assessing the structural consequences of pi-electron delocalization at a resolution of 0.001 Å. To date the 1,1-d2, trans-1-d1, and cis-1-d1 and the 1-13C1 isotopomers have been prepared. A similar synthetic path should yield the 2-d1 species; new methods should give the other isotopomers.

Research Project: Solid-State NMR and Crystallographic Study of Interactions in Cocrystals of Peptides and Denaturants

Description: Denaturants promote the unfolding of protein structures in solution. They are significant in understanding the role of solvation in protein structure. The interactions through which denaturants, such as guanidinium hydrochloride and urea, act on proteins in the liquid phase remains uncertain. We investigate these cocrystals of these denaturants and small peptides as model systems using solid-state NMR and X-ray diffraction. The changes in carbon-13 and nitrogen-15 chemical shifts between the peptide crystal and its cocrystal analog are expected to yield information about the nature of the interaction.

Description: A small number of porous coordination frameworks have been commercialized. Each of these have large pore volumes, but more importantly, they are prepared cheaply in large scale from readily available starting materials, many of which are also feedstocks for polymer manufacturing. There are long-standing concerns about the environmental fate of polymer-based products—most notably polyethylene bags—that are now being addressed by biodegradable materials prepared from natural monomers such as lactic acid. As the tenets of “green chemistry” become more widely appreciated, the feedstocks and degradation products of everyday materials are more effectively scrutinized. Fortunately, there are many natural products bearing the shape and functionality needed for the preparation of coordination frameworks, yet there are few examples of materials that exhibit porosity or other attractive properties. For instance, caffeic acid and protocatechuic acid are both common biosynthetic intermediates in plants and found naturally in humus; they are commercially available compounds, yet there are no coordination frameworks that have been constructed from them. Similarly, 5-aminolevulinic acid is the first intermediate in the synthesis of porphyrin (essential for hemoglobin and myoglobin) and can undergo a non-enzymatic dimerization-oxidation to yield 2,5-dicarboxyethylpyrazine, another promising organic ligand that has not be examined. There are several recent publications and patents describing the synthesis of 5-aminolevulinic acid from the renewal platform compound, levulinic acid.

Honors in Biology Project: Characterization of the uropygial secretions of house sparrows, European starlings, and American robins

Description: Culex pipiens, a mosquito that serves as the primary vector for West Nile virus in the eastern United States,

have been shown to have species specific preferences when feeding on birds. When given the opportunity to choose from an American robin, house sparrow, or European starling, Culex will choose the robin. There are also demonstrated preferences in terms of age in Culex feeding patterns. The objective of this research is to determine the volatile and semivolatile chemical constituents of the uropygial secretions from these three species of bird. It is beginning to be understood that the uropygial secretion’s volatile and semivolatile compounds may serve as chemical signals. This study will investigate that particular phenomenon in the context of the feeding patterns of an important disease vector.

Description: γ-D-crystallin is a dimeric protein which belongs to a family of proteins found in the lens of the eye called crystallins. Because mature lens cells lack nuclei, and to properly focus light these proteins must exist in extremely high concentrations without aggregating, crystallins are exceptionally stable. However, when we induce aggregation of γ-D-crystallin, it forms amyloid fibrils similar in structure to those implicated in Parkinson's, Alzheimer's and many other neurodegenerative diseases. By isotope labeling subunits of the protein, and leaving others unlabeled, we can study in more detail changes in the secondary and tertiary structure of the protein as it aggregates. To do this we use Fourier Transform Infared Spectroscopy (FTIR) as well as an emerging technology known as 2 Dimensional FTIR (2D-IR) which is used by our collaborating lab at the University of Wisconsin Madison. Hopefully, by labeling different parts of the protein, varying the conditions which induce aggregation, and studying different aggregation-prone mutants, we can shed some light on the early formation of amyloid fibrils.

Other interests: Cello, computer science, baking.

Dain Chatel '11 Scottsdale AZ Advisor: William Fuchsman

Research Project: Reducing Sugar Assays: Ferricyanide

Description: We are using a spectrophotometric assay to gain clues about the mechanisms involved in the oxidation of reducing sugars. By examining the change in absorbance of ferricyanide ions (carbanion scavengers) at high pH, we can tell the extent of a sugar's oxidation. From there we can examine the effects of various changes in sugar structure on the extent of reaction.

Other Interests: Writing, medicine, exercise, friends and family.

Matthew Chaves '11 Holliston, MA Advisor: Jesse Rowsell

Honors Project: Semiconducting Microporous Coordination Frameworks

Description: Coordination frameworks are currently receiving an enormous amount of attention for their potential applications in the fields of renewable energy and greenhouse gas sequestration. Tens of thousands of new crystalline structures have been reported in the past decade, some displaying record-breaking pore volumes that have been confirmed experimentally through gas adsorption measurements. It has been proposed that such materials could also be employed in small molecule sensors, but only a handful of materials have been shown to demonstrate electronic, optical or magnetic responses to adsorptives. We have recently established evidence for semiconductivity in a cobalt(II) carboxylate framework that is sensitive to adsorbed water. This material is among a family of isostructural frameworks, in which none of the other members display this property. It is hypothesized that solid solutions (i.e. mixed cation frameworks) will demonstrate varying band gaps based on composition, allowing control of the material’s response to gas molecules of interest.

The aims of the project include: (1) establishing synthetic protocols for preparing mixed metal frameworks, (2) examining differences in their optical and structural properties as a function of composition, (3) synthesizing and characterizing new members of the isostructural series using other divalent cations, and if time permits (4) developing apparatus and techniques for bulk conductivity measurements on these air-sensitive materials.

Other Interests: Brazilian Jiu Jitsu, swing dancing, cooking.

Christopher Chu '11 Chicago, IL Advisor: William Fuchsman

Research Project: Optimum Reaction Times for a Reducing Sugar Assay

Description: The behavior of reducing sugar assays is affected by the structures of reducing sugars in ways that are inconsistent with the conventional wisdom about what happens to reducing sugars in the presence of oxidizing agents. We are refining a reducing sugar assay that involves ferricyanide as oxidizing agent by determining the optimum times of reaction for different sugars

Other Interests: Anime, ping-pong, magic tricks, and general mischievousness.

Clay Easterday '11 Chardon, OH Advisor: Catherine Oertel

Honors Project: Studies of Reversible Dehydration of Basic Lead Carboxylates

Description: Description of the project: Basic lead acetate, Pb3O2(CH3COO)2·0.5H2O, is a compound that forms as a corrosion product when lead-based objects such as organ pipes are exposed to acetic acid. In our laboratory, we have recently crystallized this compound using hydrothermal synthesis and determined its three-dimensional structure. Use of variable-temperature powder X-ray diffraction showed that the compound undergoes rapid, reversible dehydration upon heating or exposure to vacuum. A full understanding of the interaction of this compound with the atmosphere is important in establishing its role in the corrosion process and in considering storage or exchange of solvents within the structure. Goals of this year’s work include determination of the structure of the dehydrated form of basic lead acetate; characterization of the dehydration behavior of basic lead maleate hydrate, a related compound that appears in the literature; and exploration of hydrothermal synthesis of additional basic lead carboxylates.

Other Interests: Biking, clouds, hiking, climbing trees, reading, poor attempts at dancing, scanning electron microscopy, spreadsheets, singing in the rain and being able to raise both eyebrows independently.

Micah Ellowitz '12 El Passo, TX Advisor: Jason Belitsky

Research Project: Melanin-Inspired Lead-Binding Coatings II

Description: While “melanin” is a well-known biochemical entity among the general public, scientists know surprisingly little about the fundamental biochemistry of melanins. Nevertheless, what is known about these fascinating nano-structured pigments suggests a range of non-biological applications. The Belitsky lab is interested in exploring the properties of melanins and synthetic analogs both to understand fundamental melanin biochemistry and to exploit these properties for environmental applications. For example, eumelanin, the black to brown human pigment, is known to bind a wide range of metals and organic compounds, suggesting applications in water purification.

Honors Project: Determination of Chemical Shift Tensor Orientation of Small Peptides Using Rotational Echo Double Resonance and Single Crystal NMR

Description: Valuable information about the secondary structure and hydrogen-bonding of biological solids is contained in the chemical shift anisotropy. We can learn about this anisotropy using solid state NMR spectroscopy, and we use the chemical shift tensor to mathematically describe this anisotropy. Rotational-echo double-resonance (REDOR) experiments are common for measuring distances between two atoms in the molecule. However, further information about the orientation of the anisotropy can be extracted from these experiments by examining the individual spinning sidebands. We study of a series of small glycine- and alanine-central tripeptides, spanning a range of secondary geometries, where we determine the orientation of carbon-13 shift tensor in the molecular frame using REDOR. These measurements will be accompanied by a set of experiments that measure the chemical shift tensor in a single crystal using single crystal NMR

Description: Complex niobium and tantalum oxides are useful as photocatalysts for processes including water-splitting. A new niobate, K2Nb2O6, and its tantalum analogue, K2Ta2O6, have recently been prepared in our laboratory using hydrothermal reactions. These compounds fall into the family of compounds known as defect pyrochlores, with the general stoichiometry A2M2O6. Each is made up of a strongly bound [M2O6]2- network associated with loosely bound, exchangeable K+ ions. The focus of this summer’s work is developing ion-exchange reaction procedures to replace K+ with other ions including H+, Ag+, and Na+. The new compounds will be characterized using powder X-ray diffraction, SEM-EDS, UV-Vis spectroscopy, and thermal analysis.

Description: Synthesis of new mesoporous materials containing an organic chelating component and an inorganic silica component. The new materials will combined with transition metals and tested as possible catalysts.

Kevin Hu '11 New York, NY Advisor: Rebecca Whelan

Honors Project: Development of an ELISA for the peptide epitopes of ovarian cancer biomarker CA125

Description: The ovarian cancer biomarker CA125 is an extremely large and complex protein, comprising dozens of smaller repeated domains that serve as the epitopes for recognition by antibodies. Recently the Whelan lab succeeded in synthesizing the most frequently occurring peptide epitope of CA125 and several important sequence variants. Structural characterization by infrared spectroscopy revealed that extent of aggregated beta-sheet formation was depending upon a single amino acid substitution (proline to serine in position 8). The objective of this study is to develop an enzyme-linked immunoassay to determine the affinity of these synthetic peptide epitopes for monoclonal antibodies with affinity for CA125 as it is found in serum. We are particularly interested in learning whether differences in antibody affinity correlate with previously described differences in structure.

Description: This project is part of an ongoing collaboration with Mary Garvin in the Oberlin College Biology Department. The uropygial secretions of some bird species contain compounds ranging from the highly volatile to the extremely nonvolatile. Birds apply the secretions to their feathers during preening. The volatile and semivolatile compounds are hypothesized to serve as chemical signals, whereas the nonvolatiles likely function in maintaining and waterproofing plumage and may also regulate the release of the more volatile constituents. Previous collaborative work between the Whelan and Garvin labs identified a set of volatile and semivolatile compounds in the uropygial secretions of the gray catbird and also established that the levels of these compounds vary with age of the bird and with season/location. The objective of the current research is to characterize the nonvolatile compounds in gray catbird uropygial secretions. To accomplish this, we are using a gas chromatography-mass spectrometry to analyze secretion samples collected from free-ranging catbirds during summer 2010.

Other Interests: Academically, I'm most interested in community environmental health- understanding environmental determinants of community health and figuring out ways to leverage this knowledge to build healthier, more sustainable communities. Besides my academic interests, I enjoy playing guitar, running, and porch-sitting.

Nathaniel Kadunce '11 Beaver, PA Advisor: Jason Belitsky

Honors Project: Eumelanin Analogue Synthesis

Description: While “melanin” is a well-known biochemical entity among the general public, scientists know surprisingly little about the fundamental chemistry of melanins. Nevertheless melanins have fascinating properties that can be exploited for non-biological applications. Eumelanin, the black to brown human pigment, is known to bind a wide range of metals and organic compounds, suggesting applications in water purification. Eumelanin is thought to be composed of organic nanoparticles derived from oligomers of dihydroxyindoles. We are using iridium- and palladium-catalyzed chemistry to produce well-defined indole oligomers as synthetic models of eumelanin, as well as biomimetic polymerization to rapidly produce eumelanin-like materials for environmental applications, including heavy metal sequestration and photodegradation of organic dye.

Other Interests: I like to play tennis, cook, hang out with people, read, and drink coffee.

Honors Project: The Effects of Differences in Reducing Sugar Structures on a Reducing Sugar Assay

Description: The behavior of reducing sugar assays is affected by the structures of reducing sugars in ways that are inconsistent with the conventional wisdom about what happens to reducing sugars in the presence of oxidizing agents. We are using a refined reducing sugar assay that involves dinitrosalicylate as oxidizing agent to examine the effects of structure on reducing capabilities and determine a mechanism more consistent with observed behaviors.

Other Interests: Horseback riding, baking, swimming, playing 'cello.

Mira Levenson '12 Burien, Washington Advisor: Rebecca Whelan

Research Project: Development of an ELISA for the peptide epitopes of ovarian cancer biomarker CA125

Description: The ovarian cancer biomarker CA125 is an extremely large and complex protein, comprising dozens of smaller repeated domains that serve as the epitopes for recognition by antibodies. Recently the Whelan lab succeeded in synthesizing the most frequently occurring peptide epitope of CA125 and several important sequence variants. Structural characterization by infrared spectroscopy revealed that extent of aggregated beta-sheet formation was depending upon a single amino acid substitution (proline to serine in position 8). The objective of this study is to develop an enzyme-linked immunoassay to determine the affinity of these synthetic peptide epitopes for monoclonal antibodies with affinity for CA125 as it is found in serum. We are particularly interested in learning whether differences in antibody affinity correlate with previously described differences in structure. Other Interests: French, Croatian, medical ethics, and any kind of dancing!

Diane Lye '10 (Dec) Singapore, Singapore Advisor: Jason Belitsky

Research Project: Melanin-Inspired Lead-Binding Coatings II

Description: While “melanin” is a well-known biochemical entity among the general public, scientists know surprisingly little about the fundamental biochemistry of melanins. Nevertheless, what is known about these fascinating nano-structured pigments suggests a range of non-biological applications. The Belitsky lab is interested in exploring the properties of melanins and synthetic analogs both to understand fundamental melanin biochemistry and to exploit these properties for environmental applications. For example, eumelanin, the black to brown human pigment, is known to bind a wide range of metals and organic compounds, suggesting applications in water purification.

Other Interests: Examining career trajectories of and extrapolating lessons from multi-capable women at the intersection of business and science/technology/arts/law, Econometrics, being a part of strategic planning committees of oncampus groups, comparing and contrasting screen-writing development of various American sci-fi series, classical music + trip-hop.

Gordon MacCullum '11 Buffalo, NY Advisor: Michael Nee

Research Project: Synthesis of Organic-Inorganic Hybrid Materials

Description: Synthesis of new mesoporous materials containing an organic chelating component and an inorganic silica component. The new materials will combined with transition metals and tested as possible catalysts.

Research Project: SelSelection and affinity characterization of a DNA aptamer for the peptide epitope of CA125”

Description: The ovarian cancer biomarker CA125 is an extremely large and complex protein, comprising dozens of smaller repeated domains that serve as the epitopes for recognition by antibodies. Recently the Whelan lab succeeded in synthesizing the most frequently occurring peptide epitope of CA125 and several important sequence variants. The objective of this research is to use these synthetic peptides as targets in the process of aptamer selection. Aptamers are single-stranded nucleic acid molecules chosen out of a large random pool of sequences by an iterative selection process in which the pool of DNA is allowed to interact with a protein or peptide target, then the DNA molecules that bind well to the target are isolated from those that do not. We are using capillary electrophoresis and laser-induced fluorescence to accomplish the selection process, and in between selection rounds, DNA is amplified by polymerase chain reaction, purified, and subjected to a single-stranding procedure to give a pool that is enriched with good binders. The final result will be a unique DNA sequence that binds with very high affinity to our peptide target. This aptamer may then be used to develop new detection methods for the peptide epitopes of CA125.

Other Interests: Water Polo, Receiving Massages, Dexter, CMF, The Way Things Work, and Inyang Udo-Inyang.

Emmanuel Magara '11 Gweru, Zimbabwe Advisor: Sean Decatur

Honors Project: Vibrational Spectroscopy of Amyloids

Description: Protein clumps known as amyloids are often bad actors inside the human body and have proven quite elusive to scientists' investigations. Amyloids play a role in neurological diseases such as Alzheimer's and Parkinson's and in many other conditions, including diabetes. They are aggregates of extended fibrils composed of misfolded proteins and polypeptides, and they are rich in β-sheets, a flat type of protein secondary structure. Most infamous and most studied among the amyloids is amyloid-β-40 (Aβ40), the one seen in the brains of Alzheimer's patients. Using infrared vibrational spectroscopy techniques, our group can follow the process all the way from monomer states of the protein or polypeptide through soluble aggregates to fibrous aggregates. We have found that there are two mechanisms of reaggregation and alignment, depending on the peptide concentration. At low concentrations, strands detach from the aggregate and reattach themselves, sometimes to a different aggregate than the one from which they broke off. At higher concentrations, strands are less inclined to break off and roam about, so rearrangement tends to be confined within a particular aggregate. At intermediate concentrations, both processes occur.

Research Project: The Effects of Differences in Reducing Sugar Structures on a Reducing Sugar Assay

Description: The behavior of reducing sugar assays is affected by the structures of reducing sugars in ways that are inconsistent with the conventional wisdom about what happens to reducing sugars in the presence of oxidizing agents. We are refining a reducing sugar assay that involves dinitrosalicylate as oxidizing agent by determining the optimum times of reaction for different sugars and then using the appropriate reaction times to examine the effects of reducing sugar structures on the assay

Description: Synthesis of new mesoporous materials containing an organic chelating component and an inorganic silica component. The new materials will combined with transition metals and tested as possible catalysts.

Other Interests: Good books, writing stories, Bible trivia, dancing, playing in pit orchestras, the unexplained.

Christine Moore '11 Burke, VA Advisor: Jason Belitsky

Research Project: Melanin-Inspired Lead-Binding Coatings I

Description: While “melanin” is a well-known biochemical entity among the general public, scientists know surprisingly little about the fundamental biochemistry of melanins. Nevertheless, what is known about these fascinating nano-structured pigments suggests a range of non-biological applications. The Belitsky lab is interested in exploring the properties of melanins and synthetic analogs both to understand fundamental melanin biochemistry and to exploit these properties for environmental applications. For example, eumelanin, the black to brown human pigment, is known to bind a wide range of metals and organic compounds, suggesting applications in water purification.

Description: This project is in collaboration with Julie Hagelin of the Swarthmore College Biology Department. Little is known about the possible role of alarm odors—chemical messengers emitted by individuals under threat or attack—in bird species, though alarm odors have been characterized in insects and in reptiles. The objective of this work is to examine feces samples from chicks that were subjected to a fear-inducing stimulus and compare these samples to those from birds that were not frightened. We will use solid-phase microextraction and gas chromatography-mass spectrometry to determine and quantify the volatile compounds in these samples.

Description: We are using a spectrophotometric assay to gain clues about the mechanisms involved in the oxidation of reducing sugars. By examining the change in absorbance of ferricyanide ions (carbanion scavengers) at high pH, we can tell the extent of a sugar's oxidation. From there we can examine the effects of various changes in sugar structure on the extent of reaction.

Other Interests: Croche, recycling and dance.

John Paddock '12 Harrison Twp, MI Advisor: William Fuchsman

Research Project: NAD(P)H Oxidation in the Absence of Protein Catalysts

Description: Examining the oxygen and pH-dependency of the oxidation of the biological reducing agent NAD(P)H and products formed in the absence of any protein catalysts.

Description: The Matlin Lab is currently carrying out intensive data collection of a multitude of carbon-based radicals using ab inito, semi-empirical methods on Gaussian software. The main goal for this year to collect a library of calculated radical stabilities for radical molecules and radical-producing reactions in order to then compare them with other computational models and experimental data. The project’s long term goal is to be able to rationalize and predict radical reactivity observed in some biological systems (i.e. site of deoxyribose radical attack and cleavage). Another special point of interest is how different basis sets and calculations, such as B3LYP 6-31G and CCSD(T), compare to experimental data and to each other.

Honors Project: Selection of a DNA aptamer with affinity for the peptide epitope of CA125

Description: The ovarian cancer biomarker CA125 is an extremely large and complex protein, comprising dozens of smaller repeated domains that serve as the epitopes for recognition by antibodies. Recently the Whelan lab succeeded in synthesizing the most frequently occurring peptide epitope of CA125 and several important sequence variants. The objective of this research is to use these synthetic peptides as targets in the process of aptamer selection. Aptamers are single-stranded nucleic acid molecules chosen out of a large random pool of sequences by an iterative selection process in which the pool of DNA is allowed to interact with a protein or peptide target, then the DNA molecules that bind well to the target are isolated from those that do not. We are using capillary electrophoresis and laser-induced fluorescence to accomplish the selection process, and in between selection rounds, DNA is amplified by polymerase chain reaction, purified, and subjected to a single-stranding procedure to give a pool that is enriched with good binders. The final result will be a unique DNA sequence that binds with very high affinity to our peptide target. This aptamer may then be used to develop new detection methods for the peptide epitopes of CA125.

Other Interests: Enjoy knitting, minesweeper and procrastination, singing, dancing, skiing, frisbee, cuddling, sleeping in the sunshine, and long walks on the beach.

Gabrielle White-Dzuro '12 Toronto, ON Advisor: Catherine Oertel

Research Project: Hydrothermal Synthesis of Network Compounds Containing Main Group Ions

Description: Hybrid inorganic-organic network materials are made up of metal atoms or clusters linked by multitopic organic ligands, which are capable of coordinating more than one metal center. Incorporating main group metals with stereoactive lone pairs (e.g. Pb2+, Sb3+) into these compounds can lead to non-centrosymmetric solids with properties including non-linear optical activity. Main group ions can also lead to interesting structural features when included in complex inorganic oxides. The focus of this summer’s work is optimization of hydrothermal synthesis of Pb2Sn2O6 and structural characterization of this complex oxide. We will also use hydrothermal methods to incorporate organic ligands into networks containing main group ions. Compounds will be characterized using powder and single-crystal X-ray diffraction, SEM-EDS, and thermal analysis.

Description: Small biological molecules, such as di- and tripeptides, lend themselves well to quantitative computational analysis, as well as experimental investigation. The small tripeptides we are studying are chains of three alanine and/or glycine amino acids. I am using a combination of computational techniques to investigate the secondary structure of these molecules in their solvated state. Molecular dynamics simulations use calculated forces and Newtonian laws of motion to map the trajectories of systems of atoms over periods of nanoseconds or picoseconds. Ab initio and semiempirical calculations numerically solve the Schrödinger equation, using quantum mechanical principles to calculate various molecular properties.